Nitric Oxide Can Be Transported In Its Free Form Along The Vascular Tree

Beside the reactions of NO with thiols and amines, a third route has been proposed for the transport of NO in plasma. In-vivo investigations with authentic NO shed light on the capability of plasma to transport NO in its free form along the vascular tree. Infusions of NO solutions into the brachial artery of human volunteers led to an increase in the diameter of the downstream artery and to an increase in forearm blood flow [4]. In these experiments, the immediate effects appeared to be mediated by bioactive NO itself and the delayed effects by plasma RSNOs. The effective lifetime of NO in blood is thought to be limited by numerous reactions in plasma and, importantly, with intraerythrocytic hemoglobin (see above). However, in flowing blood, these degradative reactions are markedly attenuated for several reasons: because of the properties of the RBC membrane, entry of NO into RBCs occurs at a rate up to three orders of magnitude slower than would be expected from simple diffusion [30,31]. Moreover, in a perfused blood vessel, the endothelial surface is in contact with an RBC-free plasma zone, which has been estimated to reach up to 25% of the luminal diameter in thickness [29]. Within this RBC-free zone of laminar flowing blood, NO has a surprisingly long half-life. Considering the concentration of dissolved oxygen in blood (~ 150-250 ^M) and assuming that physiological NO concentrations are in the nanomolar range, the biochemical lifetime of NO in such a plasma layer has been calculated to reach 100-500 s [69], provided reactions with other plasma constituents are negligible. Such a long half-life would allow NO to be transported as such from its site of synthesis to many other tissues.